New advances in the DNA damage response network of Fanconi anemia and BRCA proteins. FAAP95 replaces BRCA2 as the true FANCB protein

Cell Cycle. 2005 Jan;4(1):80-6. doi: 10.4161/cc.4.1.1358. Epub 2005 Jan 11.

Abstract

Fanconi anemia (FA) proteins function in a DNA damage response pathway that appears to be part of the network including breast cancer susceptibility gene products, BRCA1 and BRCA2. In response to DNA damage or replication signals, a nuclear FA core complex of at least 6 FA proteins (FANCA, FANCC, FANCE, FANCF, FANCG and FANCL) is activated and leads to monoubiquitination of the downstream FA protein, FANCD2. One puzzling question for this pathway is the role of BRCA2. A previous study has proposed that BRCA2 could be identical to two FA proteins: FANCD1, which functions either downstream or in a parallel pathway; and FANCB, which functions upstream of the FANCD2 monoubiquitination. Now, a new study shows that the real FANCB protein is not BRCA2, but a previously uncharacterized component of the FA core complex, FAAP95, suggesting that BRCA2 does not act upstream of the FA pathway. Interestingly, the newly discovered FANCB gene is X-linked and subject to X-inactivation. The presence of a single active copy of FANCB and its essentiality for a functional FA-BRCA pathway make it a potentially vulnerable component of the cellular machinery that maintains genomic integrity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • BRCA1 Protein / genetics
  • BRCA1 Protein / physiology*
  • BRCA2 Protein / genetics
  • BRCA2 Protein / physiology*
  • DNA Damage*
  • DNA Repair / genetics
  • DNA Repair / physiology
  • Fanconi Anemia / genetics
  • Fanconi Anemia / physiopathology*
  • Fanconi Anemia Complementation Group Proteins / genetics
  • Fanconi Anemia Complementation Group Proteins / physiology*
  • Gene Expression Regulation
  • Genes, BRCA1
  • Genes, BRCA2
  • Genes, X-Linked
  • Humans
  • Receptors, Peptide / genetics
  • Receptors, Peptide / physiology
  • Signal Transduction

Substances

  • BRCA1 Protein
  • BRCA2 Protein
  • Fanconi Anemia Complementation Group Proteins
  • Receptors, Peptide
  • anthrax toxin receptors